1. Enzymes What You Should Know, GI Function, and Autism Autism One Conference Chicago, IL May 23, 2009

2. Education and research PhD - University of South Alabama College of Medicine Academic research: UVa, St. Louis College of Medicine Cell signalling of various receptors: adenosine, opiate/cannabinoid neurobiology, diabetes Private research in Enzyme Manufacturing Developed first enzyme product targeted to autism community Found DPP IV as undocumented side activity in enzyme blends Consultant and currently owner of Houston Enzymes

3. What are enzymes? Specialized proteins that catalyze chemical reactions Not changed or destroyed during the reaction Specific for a single function Many thousands of different enzymes Metabolic - inside cells, difficult to affect Digestive - Breakdown proteins, carbohydrates, fats Pancreatic (animal) Plant-based (Fruits, fungi, bacterial)

4. Digestive enzymes Necessary to break down whole foods into absorbable form Found in saliva, stomach, pancreas and intestine Produced by probiotic bacteria in colon Both pancreatic and plant-based enzymes available in oral form Plant-derived enzymes offer advantages over pancreatic enzymes

5. Autism may affect the gut Inflammation Malabsorption Developmental delay Food allergies and other immune system problems

6. Some foods not tolerated in autism Wheat (gluten protein) Dairy (casein protein and/or lactose sugar) Soy protein Certain carbohydrates Polyphenolic compounds, oxalates, lectins

7. Restoring gut health Provide healthy environment for probiotic bacteria Reduce inflammation as well as the cause Eliminate potential future allergen production

8. Restrictive diets often helpful Gluten-free Casein-free diet (GFCF) Specific Carbohydrate Diet (SCD) Low Oxalate Diet (LOD) Body Ecology Diet (BED) Gut and Psychology Diet (GAPS)

9. Oral enzymes complement diets Many diets now incorporate oral enzyme supplements Enzymes often used as alternative to some diets Enzymes can often achieve same goals as diets More specific Faster Less costly, more convenient

10. Diets may also be difficult Nutritional Insufficiency? Family lifestyles Cost and availability

11. Observed effects of enzymes Speech starts or improves dramatically Better eye focus and contact Less stimming Improvements often noted by unknowing third parties Bowel movements improved Positive benefits often increased for those on diets Benefits are dependent upon many factors

12. How do enzymes help? Break down proteins differently, more thoroughly Prevent production of exorphin peptides Requires optimal blend of protease and peptidase enzymes Function in stomach, no peptide absorption occurs Modify polyphenolic compounds May mimic enzymes produced by probiotics? Break down carbohydrates Modify effect of stomach/pancreatic enzymes

13. -tyr-pro-phe-pro-glu-pro-ile- (1) Pepsin(2) Elastase Bovine Casein Casomorphin x-x-x-x-x-x-x-x Proteins: Digestive formation of casomorphin

14. Example: DPP IV peptidase Only known enzyme to degrade exorphin casomorphin Produced by cells in GI tract Found in commercially available protease blends (Houston, 1999)

15. DPP IV tyr-pro-phe-pro -glu-pro-ile DPP IV effect on casomorphin

16. phe-pro- (1) Pepsin Bovine Casein DPP IV In Stomach Casein amino acid sequence affected by DPP IV x-x-x-x--x-x-x-xtyr-pro-glu-pro- il e No casomorphin formed!

17. (1) Pepsin (2) Elastase tyr-pro-phe-pro-glu-pro-ile Bovine Casein Casomorphin Protease 4.5 Protease 6.0 X X Blocked peptide formation by multiple proteases -x-x-x-x pro- glu- pro-ile x-x-x-x-tyr-pro-phe-

18. Enzymes may help other foods Some indications of help with oxalates and lectins More obvious help for foods high in polyphenolics Apparent function is through modificaton of polyphenols, not degradation

19. Polyphenolic compounds Very abundant in diet, several hundred identified in foods Chief interest is due to antioxidant potential Modulate the activity of wide range of enzymes/receptors Research areas mainly focus on role in oxidative stress

20. “Phenols” are different from polyphenolics Polyphenolics contain phenol structure Phenol itself is a toxic compound Phenols can be produced by protein fermentation in the gut Sulfation pathways are the primary means of inactivating phenol Phenol sulfotransferases, found in mucosa of gut, are necessary for phenol removal Phenols and salicylates are similar compounds

21. Polyphenolics are complex and diverse compounds

22. Bioavailability of polyphenols Metabolism of polyphenols occurs via a common pathway Aglycones can be absorbed from the small intestine, however, most polyphenols are present in food in the form of esters, glycosides, or polymers that cannot be absorbed in their native form These substances must be hydrolyzed by intestinal enzymes or colonic flora before they can be absorbed Only then can polyphenols be conjugated through methylation, sulfation, and glucoronidation in the intestine and liver. This is a detoxification process that limits toxic effects and facilitates elimination through bile or urine

23. Intestinal absorption and metabolism In foods, all flavonoids except flavanols are found in glycosylated form, which prevents them from being absorbed Only aglycones and some glucosides can be absorbed in the small intestine, whereas polyphenols linked to a rhamnose, arabinose, or xylose sugar must reach the colon and be hydrolyzed by enzymes produced by the microflora before being absorbed Proanthocyanidins are very large polymers and are poorly absorbed; they may produce their effects locally in the gut Hydroxycinnamic acids are naturally esterified in plants, and humans do not have the esterase enzymes needed to allow these compounds to be absorbed. Only the colonic flora can produce the enzymes needed. Once absorbed, polyphenols are metabolized by the same pathways as drugs, hormones, and neurotransmitters

24. Enzyme dosing Experimentation encouraged, no toxicity, safe dosing Try taking enzymes at beginning of meal Base dosing on size of meal, not body weight or age May be taken with most medications or other supplements Effective with first dose for digestive results

25. Reasons to try enzymes Results often seen faster than with diet Inexpensive No special medical attention or testing required May be a better fit to a family’s lifestyle, less stress

26. Devin Houston, PhD devin.houston@houston-enzymes.com www.houston-enzymes.com 1-866-757-8627